Sudden Cardiac Death in Hypertrophic Cardiomyopathy

Abstract

Hypertrophic cardiomyopathy (HCM) is a common disorder of cardiac muscle associated with sudden cardiac death (SCD). HCM is defined by increased left ventricular wall thickness or mass, in the absence of abnormal loading conditions to account for the observed abnormality.1 In most adults, the disease is inherited as an autosomal dominant trait and is caused by mutations in cardiac sarcomere protein genes.1 Histologically, HCM is characterized by myocardial disarray, fibrosis, and small vessel disease.2 Macroscopically, the hypertrophy is typically asymmetrical and 25% of patients have resting left ventricular outflow tract obstruction (LVOTO).3 SCD in HCM is caused mainly by ventricular arrhythmias that can be effectively treated by implantable cardioverter defibrillator (ICD) therapy. Identification of patients at high risk is a cornerstone of management and research during the past 4 decades has recognized a number of phenotypic characteristics that can be used to identify those patients who might benefit from an ICD. ### Genetics and Pathogenesis In infants and children, HCM is often associated with syndromes (eg Noonan’s syndrome, LEOPARD syndrome) and metabolic diseases (eg, glycogen storage diseases).1 In adults and adolescents, HCM is primarily caused by mutations in cardiac sarcomeric protein genes, and is inherited in an autosomal dominant manner.1 Mutations in these genes can be found in ≈60% of patients, and MYBPC3 and MYH7 mutations account for the majority of cases. Genotype–phenotype correlations are weak, with significant interfamily and intrafamily phenotypic variability. Exactly how HCM develops as a consequence of sarcomere protein gene mutations is not known.4 ### Sudden Cardiac Death and Underlying Mechanisms Existing data indicate that most patients with HCM die from cardiac causes,5–7 but this may reflect referral bias from centers reporting on mortality in HCM. Although the data do not exist, based on prevalence of 1/500,8 it is likely that most patients with HCM remain …